Distribution of Major Histocompatibility Complex (MHC) in normal human skin was performed on aceton fixed frozen sections in five age groups (Fetal, Infant, Child & Adolescence, Adult and elderly ), in both sexes and in different skin sites. Both MHC class I & II expression reached their highest values in adult age group and decreased in elderly. Fetal specimens showed high value for class I and lower values for class II. Males had higher values than females, exposed skin sites had higher values than the non-exposed for class I, however, class II had higher values in non-exposed more than the exposed skin sites. Class I was present in all epidermal and dermal components, however, class II was present only in Langerhans’cells and some of the sweat glands. Class I was down regulated in melanomas, however, class II was upregulated in melanomas. Class II started to appear in dysplastic nevi and in melanomas, so it acts as a marker for atypical cells. The non- immunological functions of both class I & II was documented in this work.